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Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-04-1130. This Article Full Text (PDF) All Versions of this Article: 2003-04-1130v1 102/9/3224    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kataoka, H. Articles by Coughlin, S. R Search for Related Content PubMed PubMed Citation Articles by Kataoka, H. Articles by Coughlin, S. R Social Bookmarking                   What's this? Submitted April 10, 2003 Accepted July 2, 2003 Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells Hiroshi Kataoka, Justin R Hamilton, David D McKemy, Eric Camerer, Yao-Wu Zheng, Abby Cheng, Courtney Griffin, and Shaun R Coughlin* Cardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA * Corresponding author; email: coughlin{at}cvrimail.ucsf.edu. Defining the relative importance of protease-activated receptors for thrombin signaling in mouse endothelial cells is critical for a basic understanding of thrombin signaling in these cells and for the rational use of knockout mice to probe the roles of thrombin's actions on endothelial cells in vivo. We examined thrombin- and PAR agonist-induced increases in cytoplasmic calcium, phosphoinositide hydrolysis, ERK phosphorylation and gene transcription in endothelial cells from wild-type and PAR-deficient mice. PAR1 and PAR4 agonists triggered responses in wild-type but not in Par1-/- and Par4-/- endothelial cells, respectively. Calcium imaging confirmed that a substantial fraction of individual endothelial cells responded to both agonists. Compared to wild-type cells, Par1-/- endothelial cells showed a marked decrease in responsiveness to low concentrations of thrombin, and cells that lacked both PAR1 and PAR4 showed no responses to even high concentrations of thrombin. Similar results were obtained when endothelial-dependent vasorelaxation of freshly isolated mouse aorta was used as an index of signaling. Thus PAR1 is the major thrombin receptor in mouse endothelial cells but PAR4 also contributes. These receptors serve at least partially redundant roles in endothelial cells in vitro and in vivo and together are necessary for the thrombin responses measured. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Knezevic, M. Tauseef, T. Thennes, and D. Mehta The G protein {beta}{gamma} subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin J. Exp. Med., November 23, 2009; 206(12): 2761 - 2777. [Abstract] [Full Text] [PDF] D. F. Meoli and R. J. White Thrombin induces fibronectin-specific migration of pulmonary microvascular endothelial cells: requirement of calcium/calmodulin-dependent protein kinase II Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L706 - L714. [Abstract] [Full Text] [PDF] M. Megyeri, V. Mako, L. Beinrohr, Z. Doleschall, Z. Prohaszka, L. Cervenak, P. Zavodszky, and P. 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